This research concerns a proposed scheme in which a perturbation of the plasma membranes of epidermal cells allows calcium to enter and activate adenyl cyclase and phospholipase A, resulting in the synthesis of cAMP and prostaglandins (PGs). An example of a potential perturbing agent may be PGEl; mass spectrometric analysis of the levels and species of PGs in fresh and cultured epidermis will suggest that PGEl might originate in the dermis. In either case we will demonstrate using 3H-PGs whether or not there are receptor sites for PGs and other agents on epidermal cell membranes. Our scheme further suggests: that a specific membrane phospholipid exists rich in PG precursor fatty acids, identifiable by chromatographic analysis; that PGEl and catecholamines activate phospholipase A in the presence of Ca ions; that liberated lysophosphatide promotes Ca ions influx; that PGEl activates adenyl cyclase (as shown by the conversion in vitro of labeled ATP to cAMP) only in the presence of low Ca ions levels, but catecholamines may have a different mechanism. Within the cells, rising Ca ions concentration increased PGF levels by suppressing 15-hydroxy-PG-dehydrogenase activity and PGE synthesis (examined by the conversion of labeled polyunsaturated acids to labeled PGE and PGFs), and PGFs stimulate guanyl cyclase at certain Ca ions levels (3H-GTP yields cGMP). Thus Ca ions, PGs, cAMP levels rise simultaneously after a stimulus, followed by cGMP; these are measured by atomic absorption spectroscopy, mass spectrometry, and protein binding methods respectively. PG levels and species should vary during a cell cycle. These events serve to promote and control intracellular cyclic nucleotide concentrations, and form the subjects of research presented here. BIBLIOGRAPHIC REFERENCES: Wilkinson DI, and Walsh JT: Prostaglandin biosynthesis in the epidermis and dermis of young mouse skin, and the effect of calcium and cyclic nucleotides. J Invest Dermatol 68:210-214, 1977. Wilkinson DI, Orenberg EK, Farber EM: Effect of retinoic acid on the cyclic nucleotide content of keratinocytes in culture. J Invest Dermatol 68:238 (abstract) 1977. Presented at 38th Annual Meeting, Society for Investigative Dermatology, Washington, D.C., April 30, 1977.